The possible role of a perturbed blood-nerve barrier in the pathogenesis of certain diseases of the peripheral nervous system has been suggested but not fully explored. This research program seeks to elucidate the possible roles of a permeable blood-nerve barrier in the pathogenesis of nerve fiber damage in peripheral neuropathies. The recognized components of the blood-nerve barrier, the perineurium's diffusion barrier and the endoneurial capillaries' diffusion barrier, will be studied using horseradish peroxidase as a light- and electron-microscopic tracer. The sites and mechanisms of blood-nerve barrier breakdown in lead neuropathy (a neuropathy with primarily segmental demyelination) will be compared with the sites and mechanisms of blood-nerve barrier breakdown in isoniazid neuropathy (a neuropathy with primarily axonal degeneration). Peripheral nerves having a permeable blood-nerve barrier will be studied by light and electron microscopy to determine the pathological alterations and/or structural adaptations of nerve fibers subjected to a chronically altered blood-nerve barrier. To ascertain whether or not edema and increased endoneurial pressure can cause nerve-fiber damage, the kind and extent of nerve-fiber damage in these intoxicated animals having a perturbed blood-nerve barrier will be compared with the kind and extent of nerve-fiber damage in intoxicated animals having an initially intact blood-nerve barrier.